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Table 2 Preclinical studies using copper-64 as therapeutic agent

From: Hypoxia imaging and theranostic potential of [64Cu][Cu(ATSM)] and ionic Cu(II) salts: a review of current evidence and discussion of the retention mechanisms

TracerTumor typeResults/ConclusionsReference
[64Cu][Cu(ATSM)]Colon cancerHigh dose (370 MBq) of [64Cu][Cu(ATSM)] significantly increased the survival rate for tumor bearing animals with no acute adverse effects.[46]
[64Cu][Cu(ATSM)]Lung cancer[64Cu][Cu(ATSM)] highly accumulated in hypoxic region of the tumor and reduced the survival rate of clonogenic tumor cells in a dose-dependent manner, with observed DNA damage from copper-64 radiation.[48]
[64Cu][Cu(ATSM)]Lung cancerCells in high [64Cu][Cu(ATSM)] regions were quiescent but highly clonogenic under mild hypoxia. These cells should be attacked by either [64Cu][Cu(ATSM)] internal radiotherapy and/or other intensive-modulated radiotherapy.[19]
[64Cu][Cu(ATSM)]Breast cancer (MCF-7)Uptake of [64Cu][Cu(ATSM)] as well as radio toxicity increased with decreased atmospheric oxygen level. Statistically significant increase of [64Cu][Cu(ATSM)] DNA damage in hypoxia confirmed by Comet assay. Hypoxia-enhanced uptake of copper-64 may be used to overcome radio-resistance of hypoxic MCF-7 cells.[51]
[64Cu][Cu(ATSM)]Colon cancer[64Cu][Cu(ATSM)] treatment inhibited tumor growth and reduced tumor volume. Percentage of CD133+ cancer stem cells and metastatic ability in treated cells were decreased.[57]
[64Cu]CuCl2Brain cancer (GBM)Treatment with [64Cu]CuCl2 inhibited the neurosphere-forming ability of GBM cell lines. A therapeutic dose led to significant decreased of complete regression of tumor volume, followed by prolonged survival with no significant adverse effects observed.[29]
[64Cu][Cu(ATSM)]Colon cancer[64Cu][Cu(ATSM)] can be used to address the effects of tumor hypoxia and increased HIF-1 activation caused by repeated use of bevacizumab, which has been shown to inhibit tumor growth and prolong survival in bevacizumab-treated mice.[64]
[64Cu][Cu(ATSM)]Brain cancer (GBM)Single administration of high-dose (148 MBq) [64Cu][Cu(ATSM)] inhibited tumor growth and prolonged survival in a dose-dependent manner, with slight adverse effects. Multiple administration (4 × 37 MBq) showed optimal results for tumor inhibition and survival, with no observed adverse effects.[62]
[64Cu][Cu(ATSM)]/[64Cu]CuCl2 [64Cu][Cu(ATSM)] and [64Cu]CuCl2 shown similar in vivo accumulation in the hypoxic regions of the tumor, while [64Cu][Cu(ATSM)] also stained non-hypoxic regions with high expression of copper transporters. In vitro [64Cu][Cu(ATSM)] has siginificant higher accumulation than [64Cu]CuCl2.[68]